Radiotherapy is a common technique for treating cancerous tumors, used in approximately 50% of cases. It consists in creating free radicals in the cells by localized irradiation; these free radicals cause breaks in the DNA of the irradiated cells, resulting in their death. The efficacy of radiotherapy treatments is currently limited by the resistance of certain tumors to ionizing radiation, compared with healthy cells. A selective and effective radiosensitization of tumor cells would make it possible to significantly improve the efficacy of these treatments and to reduce the side effects on healthy tissues.
With this aim, various approaches have been described, such as the use of nanoparticles capable of locally generating free radicals, or the use of radiosensitizing agents.
The first approach consists in locally generating free radicals, within the tumor, using nanoparticles. The methods of this type described to date are based on physical properties, associated with the nanoparticles, making it possible to effectively generate free-radical species at their surface under irradiation. The nanoparticles used generally consist of atoms which have a high atomic number (Z), in order to more efficiently absorb X-rays, but they are generally expensive materials (gold, platinum, rare earth elements), and/or can induce toxicity, and/or are not very stable in a biological medium. By way of example, mention may be made of patent application US 2008/0003183 (Ting Guo), which proposes the use of nanoparticles consisting of heavy elements such as gold, capable of locally emitting Auger electrons under irradiation. This generation of electrons can be induced using X-rays having an energy that water molecules absorb only weakly, in order to generate free radicals essentially in the vicinity of the nanoparticles. However, in order to improve the colloidal stability and the biocompatibility of these nanoparticles, the grafting of molecules is often necessary, which can reduce the dose of secondary or Auger electrons transmitted to the environment of the nanoparticle, and therefore reduce the dose of free radicals generated.
According to the second approach mentioned above, new radiosensitizing molecules are currently being studied, the objective of which is to target the biological defenses specific to tumor cells (C. Begg et al, 2011). Unfortunately, these molecules cannot always be delivered into the tumor cells in vivo, thereby limiting their therapeutic use. This is in particular the case with POLQ interfering RNAs, which have recently shown great selectivity in the radiosensitization of tumor cells in vitro (Higgins at al, 2010). It may be difficult to use these interfering RNAs in vivo without a vectorization means, since their bioavailability is limited.
Various biotechnological applications are currently known for nanodiamonds, such as the vectorization and the delivery of medicaments and of interfering RNAs in tumor cells. In these applications, the nanodiamonds are used only as passive vectors. By way of example, mention may be made of patent application US 2010/0305309 (Ho et al.), relating to various processes for delivering medicaments with nanodiamonds. In this particular case, the nanodiamonds used as vectors are surface-oxidized, which gives them a negative surface charge and makes it necessary to add polymers so as to make it possible to vectorize DNA or RNA strands which also have a negative charge. These polymers can induce additional toxicity and significantly increase the size of the nanodiamonds, which can induce a greater retention in organs such as the liver or the kidneys for in vivo applications.